Metabolites of tamoxifen in animals and man: Identification, pharmacology, and significance

摘要: Over the past decade, non-steroidal antiestrogen tamoxifen has gained general acceptance for palliative treatment of breast cancer. Although there been much interest in pharmacology tamoxifen, our knowledge its metabolism laboratory animals and patients is incomplete precise mechanism action within target tissue tumor cells unknown. This review briefly describes various species patients. Several metabolites are known their relative potencies as estrogens antiestrogens compared with parent compound. Apart from monohydroxytamoxifen, none tamoxifen's more potent antiestrogens, but a metabolite dog, Metabolite E, fully estrogenic. Routine assays (tlc, HPLC, glc/ms) available to detect N-desmethyltamoxifen, newly identified metabolite, designated Y, biological fluids. Continuous therapy (10 mg bid) produces steady-state levels (100–200 ng/ml serum) 4 weeks. Levels N-desmethyltamoxifen often up twice achieved while monohydroxytamoxifen Y below 10 ng/ml. high binding affinity estrogen receptor, metabolic activation an advantage rather than requirement antiestrogenic activity. The vivo net result individual actions compound competing occupation receptors tissues tumors.